Comparative analysis of neurological disorders focuses genome-wide search for autism genes.
The behaviors of autism overlap with a diverse array of other neurological disorders, suggesting common molecular mechanisms. We conducted a large comparative analysis of the network of genes linked to autism with those of 432 other neurological diseases to circumscribe a multi-disorder subcomponent of autism. We leveraged the biological process and interaction properties of these multi-disorder autism genes to overcome the across-the-board multiple hypothesis corrections that a purely data-driven approach requires. Using prior knowledge of biological process, we identified 154 genes not previously linked to autism of which 42% were significantly differentially expressed in autistic individuals. Then, using prior knowledge from interaction networks of disorders related to autism, we uncovered 334 new genes that interact with published autism genes, of which 87% were significantly differentially regulated in autistic individuals. Our analysis provided a novel picture of autism from the perspective of related neurological disorders and suggested a model by which prior knowledge of interaction networks can inform and focus genome-scale studies of complex neurological disorders.
Wall
D P
DP
Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. dpwall@hms.harvard.edu
Esteban
F J
FJ
Deluca
T F
TF
Huyck
M
M
Monaghan
T
T
Velez de Mendizabal
N
N
Goñí
J
J
Kohane
I S
IS
D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D015870:Gene Expression; D053263:Gene Regulatory Networks / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D009422:Nervous System Diseases / Q000235:genetics*; D010802:Phylogeny; D035781:Siblings; D049490:Systems Biology